Mutation of the core region of HBV-DNA and submassive hepatic necrosis in patients with anti-HBe-positive chronic hepatitis B

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Abstract
Three patients with submassive hepatic necrosis developed acute liver failure during the severe reactivation of chronic hepatitis B. The activity of hepatitis B virus (HBV) DNA polymerase increased in all three patients immediately before the onset of hepatic failure. Liver biopsy specimens obtained before and after the episode of submassive hepatic necrosis showed progression to advanced liver cirrhosis. The nucleotide sequences of the precore and core regions of HBV-DNA were investigated in two of the three patients and in another two patients with piecemeal and bridging necrosis. The nucleotide and amino acid sequences of the HBV-DNA core region changed after reactivation in the the two patients with submassive hepatic necrosis, while the sequences in the other two patients with piecemeal necrosis remained unchanged before and after reactivation. These results suggest that the antigenicity of the HBV-DNA core region may have been changed before and after severe reactivation. Due to mutation at the core region, a different type of epitope would be expressed on the hepatocytes after submassive hepatic necrosis, which would not be a target for the cytotoxic T cell. This was evident by the continuation of the normal serum GPT for 5 and 9 years, respectively.